Due to its high sensitivity and non-destructive nature, Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development. Despite of the computational demands, data requirements, or ethical considerations, artificial intelligence (AI) and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing, feature extraction, and model optimization, which not only improves the accuracy and efficiency of Raman spectroscopy detection, but also greatly expands its range of application. AI-guided Raman spectroscopy has numerous applications in biomedicine, including characterizing drug structures, analyzing drug forms, controlling drug quality, identifying components, and studying drug-biomolecule interactions. AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics, particularly in disease early diagnosis and treatment optimization. Therefore, AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics, offering new perspectives and tools for disease treatment and pharmaceutical process control. In summary, integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities, offering innovative approaches for research and clinical applications.

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Objective:To observe the effect of early weightbearing after anterior cruciate ligament reconstruction (ACLR) on lower limb motor function, activation of the knee muscles and the stability of the knee joint.Methods:Forty-four persons who had received ACLR were divided at random into a control group and an experiment group, each of 22. In addition to conventional rehabilitation treatment after surgery, the control group underwent weightbearing training from the 8th day after the surgery, while the experimental group began weight-bearing training from the 3rd postoperative day. Both groups had their motor functioning evaluated using the International Knee Scoring Committee (IKDC) knee subjective evaluation form 3 days after the operation, and then 6 and 12 weeks later. Their pain perceptions were quantified on the same schedule using visual analogue scoring (VAS), and protractor measurements documented active range of motion (AROM). Electromyography (AEMG) of the medial head and rectus femoris muscle was also performed, and the stability of the knee joint was assessed using the KT-1000 test.Results:After the intervention, the average IKDC score, VAS score, knee extension and flexion AROMs, medial quadriceps head AEMG ratio, and rectus femoris muscle AEMG ratio improved to different degrees in the two groups. At 6 weeks the average pain score, knee extension and flexion ranges of motion, quadriceps medial head AEMG ratio, and rectus femoris AEMG ratio of the experimental group were all better than the control group′s averages. At 12 weeks the average IKDC subjective knee function score in the experimental group was also superior.Conclusions:Supplementing conventional rehabilitation with early weight-bearing can significantly improve the recovery from anterior cruciate ligament reconstruction. Beginning on day 3 after the operation gives the best results.

OBJECTIVES: Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer, with highmorbidity and mortality rate. Nove drug development for NSCLC is urgently needed.This study aims to investigate the activity of lathyrol derivatives and the mechanism for its inhibitory effect on the growth of NSCLC cells. METHODS: Three lathyrol derivatives were synthesized from lathyrol and their structures were verified by nuclear magnetic resonance. MTT assay was used to detect the effects of the lathyrol derivatives on the proliferation activity of NSCLC cells (A549 and H1299 cells), and the compound with the best activity was selected for subsequent experiments. Colony forming assay, wound-healing assay, and transwell assay were applied to detect in vitro cell proliferation, migration and invasion ability in A549 and H1299 cells, respectively. Quantitative real-time RT-PCR and Western blotting were performed to detect mRNA and protein levels of E-cadherin, N-cadherin, β-catenin, and MMP2 in A549 cells, respectively. RESULTS: Three lathyrol derivatives inhibited the growth of A549 and H1299 cells in a dose-dependent manner, and they showed a weak inhibitory effect on normal cells Beas-2B and 16HBE, indicating that they possessed certain selective toxic effects. Therefore, C-5 benzoylated lathyrol with the best activity was selected as the ideal drug for the subsequent experiments. Compared with the control group, the number and size of cell clusters in the treatment group of A549 and H1299 cells were significantly decreased, the relative mobility were significantly decreased, and the number of invaded cells were significantly decreased (all P<0.05), indicating that the in vitro cell proliferation, migration and invasion ability were decreased. The mRNA levels of integrin α2, integrin β1, MMP2, MMP9, β-catenin, and N-cadherin were decreased, while the expression of E-cadherin was increased (all P<0.05). The protein levels of N-cadherin, β-catenin, MMP2, and integrin αV were decreased, while the expression of E-cadherin was increased (all P<0.05). CONCLUSIONS The lathyrol derivatives synthesized in this study possess good inhibitory activity against NSCLC. Among them, C-5 benzoylated lathyrol significantly inhibits the proliferation, migration, and invasion ability of NSCLC cells in vitro through regulating the process of epithelial-mesenchymal transition.
Cadherins/genetics* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; Lung Neoplasms/drug therapy* ; Matrix Metalloproteinase 2/genetics* ; RNA, Messenger ; beta Catenin/genetics*

By analyzing the physiological structure and motion characteristics of human ankle joint, a four degree of freedom generalized spherical parallel mechanism is proposed to meet the needs of ankle rehabilitation. Using the spiral theory to analyze the motion characteristics of the mechanism and based on the method of describing the position with spherical coordinates and the posture with Euler Angle, the inverse solution of the closed vector equation of mechanism position is established. The workspace of mechanism is analyzed according to the constraint conditions of inverse solution. The workspace of the moving spherical center of the mechanism is used to match the movement space of the tibiotalar joint, and the workspace of the dynamic platform is used to match the movement space of subtalar joint. Genetic algorithm is used to optimize the key scale parameters of the mechanism. The results show that the workspace of the generalized spherical parallel mechanism can satisfy the actual movement space of human ankle joint rehabilitation. The results of this paper can provide theoretical basis and experimental reference for the design of ankle joint rehabilitation robot with high matching degree.
Ankle Joint ; Biomechanical Phenomena ; Humans ; Movement ; Range of Motion, Articular

Objective:To explore the effects of aerobic exercise combined with resistance exercise on patients with diabetic peripheral neuropathy (DPN).Methods:A total of 60 patients with DPN in Sixth Affiliated Hospital of Nantong University from June 2018 to October 2019 were selected, and randomly divided into control group (20 cases), aerobic exercise group (20 cases) and combined training group (20 cases). Three groups all received the routine medication management and dietary guide. The control group had no other intervention. The aerobic exercise group received moderate intensity cycle ergometer, 40 min/time, once a day, three times a week. In addition to the moderate intensity aerobic exercise, patients in the combined training group conducted resistance exercise with elastic belt, 40 min/time, once a day, three times a week. The curative effect was evaluated after 12 weeks, which included fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), nerve conduction velocity and static balance function of eye-opened and eye-closed condition in Pro-Kin 254 balance assessment equipment.Results:Before exercise intervention, there were no significant differences in any measurements among the three groups (all P>0.05). After exercise intervention, the FBG, HbA1c, motor nerve conduction velocity of common peroneal nerve, sensory nerve conduction velocity of common peroneal nerve, sway length and area in the eye closed test of Pro-Kin254 balance assessment in the aerobic exercise group were significantly better than those in the control group[(6.26±0.28) vs. (6.76±0.68) mmol/L, (5.75±0.42)% vs. (6.48±0.37)%, (45.36±8.78) vs. (42.16±6.78) m/s, (38.75±8.14) vs. (35.45±8.34) m/s, (513±39) vs. (613±71) mm, (678±58) vs. (1 024±98) mm 2] (all P<0.05); the above indexes of the combined training group [(6.03±0.36) mmol/L, (5.27±0.35)%, (49.51±9.76) m/s, (42.87±7.18) m/s, (425±38) mm, (535±47) mm 2] were significantly better than those in the other two groups, the sway length and area in the eye open test of Pro-Kin254 balance assessment were also significantly superior to those in the other two groups [(316±21) vs. (395±18), (436±28) mm and (689±33) vs. (782±30), (824±70) mm 2] (all P<0.05). Conclusion:Aerobic exercise combined with resistance exercise can better improve the levels of blood glucose and HbA1c, increase nerve conduction rate and improve static balance ability compared with simple aerobic exercise in patients with DPN.

Objective:To investigate the risk factors for delayed gastric emptying (DGE) following pancreaticoduodenectomy (PD).Methods:Clinical data of 385 patients who underwent PD in Changhai Hospital of Navy Medical University from January 2017 to November 2017 were retrospectively analyzed, including 235 men and 150 women. According to the definition of DGE by the International Study Group of Pancreatic Surgery (ISGPS), patients were divided into-clinically irrelevant DGE (non CR-DGE) group and clinically relevant DGE(CR-DGE) group. Univariate analysis and multivariate logistic analysis were used to identify the risk factors of CR-DGE after PD.Results:Of the 385 patients, 78 cases (20.3%) developed DGE. There were 35 cases of CR-DGE (9.1%). In the multivariate analysis, BMI( OR=1.117, 95% CI1.006-1.240, P=0.038), preoperative serum albumin( OR=0.902, 95% CI 0.832-0.977, P=0.012), the main pancreatic duct diameter (MPD)≤3 mm( OR=2.397, 95% CI 1.016-5.653, P=0.046), soft texture of pancreas( OR=2.834, 95% CI 1.093-7.350, P=0.032), clinically relevant postoperative pancreatic fistula (CR-POPF)( OR=4.498, 95% CI 1.768-11.441, P=0.002) were independent risk factors for CR-DGE after PD. Conclusions:High BMI, low preoperative serum albumin, MPD ≤3 mm, soft texture of pancreas and CR-POPF after surgery were independent risk factors for CR-DGE, and early clinical interventions should be performed.

Objective To investigate the effects of radical prostatectomy on the overall survival (OS)and tumor-specific survival in prostate cancer(PCa)patients aged 75 years and older.Methods Clinical data of patients aged 75 and older with localized PCa from Surveillance,Epidemiology,and End Results(SEER)Database from 2004 to 2016 were retrospectively analyzed.There were 17 899 cases of PCa undergoing radical prostatectomy and 3 648 cases of PCa without surgery in this study.The OS and prostate cancer-specific survival(PSS)were compared between the surgery group and the nonsurgery group.Results For 75-79-year-old patients with high-risk localized PCa,the OS and PSS in the surgery group were better than in the non-surgery group (OR =1.49,95 ％ CI:1.22 ～ 1.82,P ＜ 0.01;OR=1.43,95％CI:1.09～2.04,P＜0.05).For patients aged 75-79 years with low-risk PCa and patients aged 80 years and older with low-,middle-,or high-risk PCa,the OS was worse in the surgery group than in the non-surgery group(OR =0.54,95％CI:0.38～0.76,P＜0.01;OR =0.47,95％CI:0.34～0.66,P＜0.01;OR =0.58,95％CI:0.44～0.78,P＜0.01;OR =0.59,95％CI:0.51 ～0.68,P＜0.01).For patients aged 75-79 years with low-or medium-risk PCa and patients aged 80 years and older with medium-risk PCa,there was no statistical difference in PSS between the surgery and non-surgery groups(P＞0.05).Conclusions Age limits for prostatectomy should be extended as a result of increasing average life expectancy.Patients aged 75-79 years with high-risk PCa can be considered for surgical treatment,while it should not be recommended for patients aged 75-79 years with low-or medium-risk localized PCa or aged more than 80 years.Many factors should be considered in making treatment decisions for prostate cancer.

Urate oxidase (Uox), an enzyme catalyzing oxidation of uric acid to allantoin, is widely used as diagnostic reagents and for treatments of uarthritis and hyperuricemia diseases. In our study, a higher Uox producer, bacterial strain OUC-1, was isolated from soil samples. The 16S rRNA gene sequence of strain OUC-1 showed 99% identity to the homologous fragments of Bacillus fastidiosus. After purification, Uox showed the optimal pH and temperature was 10.0 and 40 °C. The Km value of Uox was (0.15±0.04) mmol/L (n=5) with uric acid as the substrate. Uox activity was enhanced by Mg²⁺, and seriously inhibited by Zn²⁺ and SDS. Then the uox gene of B. fastidiosus OUC-1 was amplified and sequenced. The 3D structures of Uox, predicted with SWISS-MODEL, showed a homotetramer structure with a subunit molecular weight of 35.38 kDa. Finally, the gene coding for the B. fastidiosus Uox was successfully cloned and heterologously expressed in E. coli, which provides theoretical basis and technical support for improvement of Uox in the future.

Objective:To determine the equilibrium solubility and the apparent oil/water partition coefficients of nicotinate-curcu-min ester,so as to provide basis for the new formula design. Methods:Nicotinate-curcumin ester was dissolved in buffer solution with pH of 1.2-7.8. HPLC was used to detect the equilibrium solubility of nicotinate-curcumin ester in various solutions. The apparent oil/water partition coefficients in octanol-water and octanol-buffer solution system were measured by a shaking-flask method. Results:The solubility of nicotinate-curcumin ester in pH 6.8 was the highest. The apparent oil-water partition coefficients of nicotinate-curcumin ester in pH 1.2,5.8,6.5 and 7.8 were lgPapvalues within the range(lgPap=1.69-1.98) beneficial to the absorption in vivo. But in pH 2,5 and 6.8,the lgPapvalues were greater than 2 with strong lipophilicity. Conclusion:The equilibrium solubility as well as ap-parent oil/water partition coefficients of nicotinate-curcumin ester is greatly influenced by the pH value of media. In the pH value with relatively high solubility,lipophilicity is stronger,suggesting it is difficult to be absorbed by the body and needs to be further studied on dosage forms.